睡眠剥夺或束缚应激对小鼠刺激-反应/习惯记忆形成及提取的影响  

Effect of sleep deprivation or restraint stress on the formation and retrieval of stimulus-response/habit memory

作　　者：郭彤 王炳昕 王采玲 宋大可 吴宁 李锦 GUO Tong;WANG Bing-xin;WANG Cai-ling;SONG Da-ke;WU Ning;LI Jin(Nanjing University of Chinese Medicine, Nanjing 210023, China;Beijing Key Laboratory of Neuropsychopharmacology,State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academyof Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China)

机构地区：[1]南京中医药大学,南京210023 [2]军事科学院军事医学研究院毒物药物研究所、抗毒药物与毒理学国家重点实验室、神经精神药理学北京市重点实验室,北京100850

出　　处：《国际药学研究杂志》2019年第1期57-64,共8页Journal of International Pharmaceutical Research

基　　金：国家重点研发计划资助项目(2016YFC0800907)

摘　　要：目的研究模拟现实环境的睡眠剥夺或束缚应激对小鼠刺激-反应/习惯记忆形成及提取的影响。方法 SPF级雄性C57BL/6小鼠,按体质量或训练结果均衡分为正常对照组、睡眠剥夺组、束缚2 h组和束缚12 h组。利用小鼠操作行为习惯化模型,采用快速眼动(REM)睡眠剥夺和束缚应激刺激模拟现实环境和特殊任务中的睡眠缺失和狭小空间状态,研究应激对小鼠习惯记忆形成及提取的影响;通过酶联免疫吸附法(ELISA)检测小鼠血浆皮质酮水平,评价下丘脑-垂体-肾上腺轴(HPA)激活的终点反应。结果与正常对照组相比,睡眠剥夺、束缚2 h和束缚12 h组小鼠的血浆皮质酮水平均显著升高(分别为P<0.01、P<0.05和P<0.05),慢性REM睡眠剥夺组小鼠操作反应习惯化行为的形成明显抑制(P<0.05),而慢性束缚应激不影响小鼠操作反应习惯化行为的形成(P>0.05);急性束缚12 h组小鼠操作反应习惯化行为的表达明显抑制(P<0.01),而急性REM睡眠剥夺不影响小鼠操作反应习惯化行为的表达。结论慢性REM睡眠剥夺抑制小鼠习惯记忆的形成、急性REM睡眠剥夺不影响小鼠习惯记忆的提取;而急性束缚应激抑制小鼠习惯记忆的提取,慢性束缚应激对小鼠习惯记忆的形成无影响。Objective To investigate the effect of stress induced by the sleep deprivation or restraint on the formation and retrieval of stimulus-response/habit memory. Methods Male C57BL/6 mice(specific pathogen free animal)were equally divided into normal control group,rapid eye movement(REM)sleep-deprivation group,2 h restraint group,and 12 h restraint group according to the body mass or outcome of training. The instrumental behavior model was used to establish habitual behavior in mice. The REM sleep deprivation and the restraint were used to simulate sleep deficits and confined space situation in real-world environments and special tasks,respectively. The end-point activation of the hypothalamic-pituitary-adrenal axis(HPA)in mice was evaluated by the concentration of plasma corticosterone which was detected by enzyme-linked immunosorbent assay(ELISA). Results Compared with the normal control group,the concentration of plasma corticosterone was significantly increased in REM-sleep-deprivation group,2 h restraint group and 12 h restraint group(P<0.01,P<0.05,and P<0.05). The formation of habitual behavior in mice was significantly inhibited(P<0.05)in chronic REM-sleep-deprivation but not in chronic restraint(2 or 12 h restraint)(P>0.05). The expression of habitual behavior in mice was significantly inhibited(P<0.01)in the acute restraint group(12 h)but not in the acute REM-sleep-deprivation. Conclusion Chronic REM sleep deprivation inhibits the formation,but not the retrieval of habit memory in mice,whereas acute restraint inhibits the retrieval,rather than the formation of habit memory.

关 键 词：睡眠剥夺 束缚 刺激-反应/习惯记忆 血浆皮质酮 

分 类 号：R338.64[医药卫生—人体生理学]